Tyrosine-protein kinase Fyn
Also known as: FYN
Function
Non-receptor tyrosine-protein kinase that plays a role in many biological processes including regulation of cell growth and survival, cell adhesion, integrin-mediated signaling, cytoskeletal remodeling, cell motility, immune response and axon guidance. Inactive FYN is phosphorylated on its C-terminal tail within the catalytic domain. Following activation by PKA, the protein subsequently associates with PTK2/FAK1, allowing PTK2/FAK1 phosphorylation, activation and targeting to focal adhesions. Involved in the regulation of cell adhesion and motility through phosphorylation of CTNNB1 (beta-catenin) and CTNND1 (delta-catenin). Regulates cytoskeletal remodeling by phosphorylating several proteins including the actin regulator WAS and the microtubule-associated proteins MAP2 and MAPT. Promotes cell survival by phosphorylating AGAP2/PIKE-A and preventing its apoptotic cleavage. Participates in signal transduction pathways that regulate the integrity of the glomerular slit diaphragm (an essential part of the glomerular filter of the kidney) by phosphorylating several slit diaphragm components including NPHS1, KIRREL1 and TRPC6. Plays a role in neural processes by phosphorylating DPYSL2, a multifunctional adapter protein within the central nervous system, ARHGAP32, a regulator for Rho family GTPases implicated in various neural functions, and SNCA, a small pre-synaptic protein. Involved in reelin signaling by mediating phosphorylation of DAB1 following reelin (RELN)-binding to its receptor (By similarity). Participates in the downstream signaling pathways that lead to T-cell differentiation and proliferation following T-cell receptor (TCR) stimulation. Phosphorylates PTK2B/PYK2 in response to T-cell receptor activation. Also participates in negative feedback regulation of TCR signaling through phosphorylation of PAG1 and PDCD1. Phosphorylation of PAG1 promotes interaction between PAG1 and CSK and recruitment of CSK to lipid rafts. Phosphorylation of PDCD1 leads to the recruitment of PTPN11/SHP-2 that mediates dephosphorylation of key TCR proximal signaling molecules. CSK maintains LCK and FYN in an inactive form (By similarity). Promotes CD28-induced phosphorylation of VAV1. In mast cells, phosphorylates CLNK after activation of immunoglobulin epsilon receptor signaling (By similarity). Can also promote CD244-mediated NK cell activation.
Classification
- Family (Pfam)
- PF07714 PK_Tyr_Ser-Thr, PF00017 SH2, PF00018 SH3_1
- InterPro
- Fyn/Yrk_SH2, Fyn/Yrk_SH3, Kinase-like_dom_sf, Non-receptor_tyrosine_kinases, Prot_kinase_dom, Protein_kinase_ATP_BS, Ser-Thr/Tyr_kinase_cat_dom, SH2, SH2_dom_sf, SH3-like_dom_sf, SH3_domain, Tyr_kinase_AS, Tyr_kinase_cat_dom
- Functional cluster
- Protein Serine/Threonine Kinases
Experimental structures · PDB · 52
- 1A0N NMR
- 1AOT NMR
- 1AOU NMR
- 1AVZ X-ray 3.00A
- 1AZG NMR
- 1EFN X-ray 2.50A
- 1FYN X-ray 2.30A
- 1G83 X-ray 2.60A
- 1M27 X-ray 2.50A
- 1NYF NMR
- 1NYG NMR
- 1SHF X-ray 1.90A
- … and 40 more
A predicted model is available from AlphaFold.
Gene Ontology · 89
- GO:0005884 actin filament
- GO:0044297 cell body
- GO:0005829 cytosol
- GO:0030425 dendrite
- GO:0005768 endosome
- GO:0097386 glial cell projection
- GO:0098978 glutamatergic synapse
- GO:0045121 membrane raft
- GO:0005739 mitochondrion
- GO:0005634 nucleus
- GO:0043204 perikaryon
- GO:0097038 perinuclear endoplasmic reticulum
- GO:0048471 perinuclear region of cytoplasm
- GO:0005886 plasma membrane
- GO:0014069 postsynaptic density
- GO:0099092 postsynaptic density, intracellular component
- GO:0098685 Schaffer collateral - CA1 synapse
- GO:0043014 alpha-tubulin binding
- GO:0005524 ATP binding
- GO:0042609 CD4 receptor binding
- GO:0042610 CD8 receptor binding
- GO:0097718 disordered domain specific binding
- GO:0019899 enzyme binding
- GO:0046875 ephrin receptor binding
- GO:0001664 G protein-coupled receptor binding
- GO:0070851 growth factor receptor binding
- GO:0042802 identical protein binding
- GO:0046872 metal ion binding
- GO:0004715 non-membrane spanning protein tyrosine kinase activity
- GO:0051428 peptide hormone receptor binding
- GO:0043548 phosphatidylinositol 3-kinase binding
- GO:0016004 phospholipase activator activity
- GO:0043274 phospholipase binding
- GO:0004713 protein tyrosine kinase activity
- GO:0097110 scaffold protein binding
- GO:0005102 signaling receptor binding
- GO:0042608 T cell receptor binding
- GO:0048156 tau protein binding
- GO:0050321 tau-protein kinase activity
- GO:0044325 transmembrane transporter binding
- GO:0031802 type 5 metabotropic glutamate receptor binding
- GO:0002250 adaptive immune response
- GO:0007411 axon guidance
- GO:0006816 calcium ion transport
- GO:0030154 cell differentiation
- GO:0007169 cell surface receptor protein tyrosine kinase signaling pathway
- GO:1904646 cellular response to amyloid-beta
- GO:1905430 cellular response to glycine
- GO:0071363 cellular response to growth factor stimulus
- GO:0070301 cellular response to hydrogen peroxide
- GO:1905232 cellular response to L-glutamate
- GO:0071375 cellular response to peptide hormone stimulus
- GO:0097062 dendritic spine maintenance
- GO:0048013 ephrin receptor signaling pathway
- GO:0038096 Fc-gamma receptor signaling pathway involved in phagocytosis
- GO:0007631 feeding behavior
- GO:0007216 G protein-coupled glutamate receptor signaling pathway
- GO:0003015 heart process
- GO:0035556 intracellular signal transduction
- GO:0007612 learning
- GO:0050900 leukocyte migration
- GO:0050804 modulation of chemical synaptic transmission
- GO:0030101 natural killer cell activation
- GO:0016525 negative regulation of angiogenesis
- GO:1902951 negative regulation of dendritic spine maintenance
- GO:2001240 negative regulation of extrinsic apoptotic signaling pathway in absence of ligand
- GO:0010629 negative regulation of gene expression
- GO:0010730 negative regulation of hydrogen peroxide biosynthetic process
- GO:0002862 negative regulation of inflammatory response to antigenic stimulus
- GO:0043524 negative regulation of neuron apoptotic process
- GO:1902176 negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway
- GO:0050868 negative regulation of T cell activation
- GO:0050860 negative regulation of T cell receptor signaling pathway
- GO:0018108 peptidyl-tyrosine phosphorylation
- GO:0051897 positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
- GO:1905477 positive regulation of protein localization to membrane
- GO:0090314 positive regulation of protein targeting to membrane
- GO:0038026 reelin-mediated signaling pathway
- GO:1905664 regulation of calcium ion import across plasma membrane
- GO:0008360 regulation of cell shape
- GO:1900449 regulation of glutamate receptor signaling pathway
- GO:1904645 response to amyloid-beta
- GO:0042220 response to cocaine
- GO:0000304 response to singlet oxygen
- GO:0009410 response to xenobiotic stimulus
- GO:0002223 stimulatory C-type lectin receptor signaling pathway
- GO:0031295 T cell costimulation
- GO:0050852 T cell receptor signaling pathway
- GO:0048010 vascular endothelial growth factor receptor signaling pathway
Drugs targeting this protein · 6
- DASATINIB ANHYDROUS inhibitor
- ILORASERTIB inhibitor
- JNJ-26483327 inhibitor
- XL-228 inhibitor
- TG100-801 inhibitor
- ENMD-981693 inhibitor
Neighborhood · nearest proteins
Related proteins · sequence + function similarity
- Tyrosine-protein kinase Fyn 1.00
- Tyrosine-protein kinase Fyn 1.00
- Tyrosine-protein kinase Fyn 1.00
- Tyrosine-protein kinase Fyn 1.00
- Tyrosine-protein kinase Fyn 1.00
- Tyrosine-protein kinase fyna 0.99
- Tyrosine-protein kinase Fyn 0.99
- Tyrosine-protein kinase fynb 0.99
- Tyrosine-protein kinase Fyn 0.99
- Tyrosine-protein kinase Yes 0.97
- Tyrosine-protein kinase Yes 0.97
- Proto-oncogene tyrosine-protein kinase Yrk 0.97
Co-cited proteins · studied together in the literature
- Tyrosine-protein kinase Fyn 1 shared papers
- Kin of IRRE-like protein 1 1 shared papers
- Microtubule-associated protein 2 1 shared papers
- Short transient receptor potential channel 6 1 shared papers
- Middle T antigen 1 shared papers
- Natural killer cell receptor 2B4 1 shared papers
- Adhesion molecule nephrin 1 shared papers
- Rho GTPase-activating protein 32 1 shared papers
- Tyrosine-protein kinase Lck 6 shared papers
- Dihydropyrimidinase-related protein 2 1 shared papers
- Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 2 1 shared papers
- Actin nucleation-promoting factor WAS 1 shared papers
Literature · 60 cited papers
- Interaction of SHP-2 SH2 domains with PD-1 ITSM induces PD-1 dimerization and SHP-2 activation. Commun. Biol. · 2020
- ARAP, a novel adaptor protein, is required for TCR signaling and integrin-mediated adhesion. J. Immunol. · 2016
- Toward a comprehensive characterization of a human cancer cell phosphoproteome. J. Proteome Res. · 2013
- T cell protein tyrosine phosphatase attenuates T cell signaling to maintain tolerance in mice. J. Clin. Invest. · 2011
- Src kinase phosphorylates RUNX3 at tyrosine residues and localizes the protein in the cytoplasm. J. Biol. Chem. · 2010
- Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci. Signal. · 2010
- The T cell receptor-mediated phosphorylation of Pyk2 tyrosines 402 and 580 occurs via a distinct mechanism than other receptor systems. J. Leukoc. Biol. · 2010
- Identification of SH3 domain interaction partners of human FasL (CD178) by phage display screening. BMC Immunol. · 2009
- Semaphorin3A signaling mediated by Fyn-dependent tyrosine phosphorylation of collapsin response mediator protein 2 at tyrosine 32. J. Biol. Chem. · 2009
- Large-scale proteomics analysis of the human kinome. Mol. Cell. Proteomics · 2009
- Phosphorylation of nephrin triggers Ca2+ signaling by recruitment and activation of phospholipase C-{gamma}1. J. Biol. Chem. · 2009
- Human protein factory for converting the transcriptome into an in vitro-expressed proteome. Nat. Methods · 2008
- … and 48 more in the literature graph